CIRCADIAN ASPECTS OF ACETYLSALICYLIC-ACID INDUCED INJURY AND PROTECTIVE EFFECT OF RANITIDINE ON THE UPPER GASTROINTESTINAL-TRACT

In a randomised parallel double-blind study the gastric and duodenal e ffects of 300 mg acetylsalicylic acid (ASA, CAS 50-78-2) daily in the presence and absence of 150 mg ranitidine (Zantic(R), CAS 66357-35-5) daily was evaluated in 32 healthy volunteers undergoing upper gastroin testinal endoscopy. Drugs were taken over a period of 7 days either at 8 a.m. (n = 16) or at 8 p.m. (n = 16). Endoscopic controls were perfo rmed at entry and repeated after 7 days of treatment. At entry both gr oups showed comparable mucosal damages: 8 a.m. group: ASA/placebo 0.8 +/- 0.1 (stomach) and 0.1 +/- 0.1 (duodenum): ASA/ranitidine 1.0 +/- 0 .0 (stomach) and 0.07 +/- 0.06 (duodenum). 8 p.m. group: ASA/placebo 0 .9 +/- 0.06 (stomach) and 0.1 +/- 0.09 (duodenum). ASA/ranitidine 0.8 +/- 0.08 (stomach) and 0.07 +/- 0.06 (duodenum). After 7 days of treat ment the lesions score increased in the ASA/Placebo group in the 8 a.m . group to 9.1 +/- 1.1 (stomach) and 2.7 +/- 1.0 (duodenum), and in th e 8 p.m. group to 10.9 +/- 1.1 (stomach) and to 3.9 +/- 0.9 duodenum). The corresponding values in the ASA/ranitidine group were 2.6 +/- 0.8 (stomach) and 0.2 +/- 0.08 (duodenum) (8 a.m.) and 4.8 +/- 0.8 (stoma ch) and 0.3 +/- 0.1 (duodenum) (8 p.m.). There was no statistical diff erence between the morning- and the evening dose of ASA. In addition, ranitidine protection was also time-independent. These data suggest th at the damaging effects of ASA as well as the protection afforded by r anitidine are independent of the time of the drug ingestion.